Recent research has shown that the periventricular tissue of the anteroventral third cerebral ventricle (AV3V) is critical for regulation of plasma volume. However, the mechanisms and additional central nervous system sites which maintain plasma volume are not known. The proposed research projects will further characterize the role of the AV3V region in plasma volume control, elucidate the mechanisms of central control of plasma volume, and determine additional CNS substrates which regulate plasma volume. The specific aims are to determine: 1) the extent of plasma volume depletion and acute physiological responses following AV3V lesions; 2) the effects of AV3V ablation on microvascular hemodynamics; 3) the effects of plasma volume restoration on natriuresis following AV3V ablation; 4) other CNS areas involved in plasma volume regulation; 5) the role glucocorticoids in plasma volume maintenance after AV3V lesions; 6) if AV3V tissue is critical for plasma volume restoration following hemorrhage, and 7) if electrical stimulation of AV3V tissue alters plasma volume and microvascular hemodynamics. Plasma volume and extracellular fluid volume will be measured using radioisotope tracers after specific CNS lesions or control surgeries. In addition, plasma concentrations of renin, corticosterone, and aldosterone will be determined by radioimmunoassay following several experimental treatments. Other experimens are designed to directly measure microvascular hemodynamics and capillary permeability following AV3V ablation, hemorrhage, or AV3V stimulation using intravital microscopic techniques. In addition, natriuretic, renal, and pressor responses will be tested in AV3V-lesioned rats following restoration of plasma volume. Finally, the role of AV3V periventricular tissue in plasma volume restitution after hemorrhage will be tested. The long term objecties of this research project are to determine the sites and physiological mechanisms through which the AV3V region regulates plasma volume. This relates directly to understanding the role of the brain in cardiovascular homeostasis. Data from these projects will increase our understanding of cardiovascular regulation and mechanisms involved in hypertension, regulation of renal function, essential hypernatremia, and restitution of blood volume following hemorrhage.